I remind you that any medical information provided in these
reports is just that…information only!! Not medical advice!! I am
not your doctor, and decisions about your health require
consultation with your trusted personal physicians and consultants.

The information I provide you is to empower you with knowledge,
and I have repeatedly asked you to be the team leader for your OWN
healthcare concerns. You should never act on anything you read in
these reports. I have encouraged you to seek the advice of your
physicians regarding health issues. Feel free to share this
information with family and friends, but remind them about this
being informational only. You must be proactive in our current
medical environment.

Don’t settle for a visit to your doctor without them giving you
complete information about your illness, the options for treatment,
care instructions, possible side effects to look for, and plans for
follow up. Be sure the prescriptions you take are accurate
(pharmacies make mistakes) and always take your meds as prescribed.
The more you know, the better your care will be, because your
doctors will sense you are informed and expect more out of them with
every visit. Always write down your questions before going for a
visit. Thanks!! Dr. Sam

Hurricanes--A note of thanksgiving and prayers

We are all so thankful that Harvey and Irma have left us, but there
are millions of Americans suffering from loss of one or more kinds.
Many of us felt the power of prayer was the answer for the lessening
of the Florida hurricane that could have devastated the entire
state. We all know how much more severe it could have been.
Prayers for all who are suffering and their families, to the first
responders, our supportive state and federal governments who were
there from the beginning and will continue to help residents.
There is no country that can reach out like the USA. I hope you
donated to the cause. Uniting and focusing on helping each other is
what our country is all about.

I feel compelled to report on a recent article in the NEJM-Journal
Watch (New England Journal of Medicine) regarding the value of
primary care physicians getting involved with genome testing for the
average low risk patient without a significant family history of a
disease. The NEJM states-“unless a person has a strong family
history of a disease or disorder, there is little value in opening
up the issue of certain genetic tendencies in a person”.

Doing genetic testing is serious business, and when someone gets
genetic information and it opens up a serious concern for that
family creating potential anxiety.

Primary care physicians are not trained to discuss this
information with their patients. In fact, there are few physicians
outside of those who specialize in genetic disease that can give a
person the proper information they need to proceed with an intensive
investigation.

The cost for an individual to get whole genome testing is about
$1000. There are websites that will give you genetic information
without any explanation or guidance, so be careful where you get
your information.

Genetic counselors are scarce (only in major university medical
centers), and they are the only specialized professionals that can
guide a person or family through the maze of investigating a
particular positive genetic test. Most of these genetic counselors
are inundated with pediatric genetic patients and their families,
and there is an extreme shortage.

If, however, there is a disease or
disorder that runs in a family, it is suggested that genomic
evaluation be considered.

Discuss this with your primary care physician and make an educated
decision about a referral for genetic testing. Ref. NEJM Journal
Watch, July 17,2017

25 million Americans have obstructive sleep apnea
and that is based on 1990s statistics. It is estimated that 26% of
Americans between the ages of 30 and 70 have OSA. With the obesity
epidemic occurring in this country, it has escalated the number of
sufferers in adults and now in children and adolescents (20% are
overweight).

As high as 85% of patients do not know they have OSA.
Even with that statistic climbing, the USPSTF (US Preventive
Services Task Force) does not recommend routine screening for sleep
apnea in the normal population. The question is what is becoming
“normal” in this country? However, if overweight and a snorer, a
sleep study should be discussed with the doctor.

B. Definition

OSA is by far the most common type of
apnea
(the majority), and is defined as
cessation of breathing for 10 seconds or longer in the face of a
respiratory effort to take a breath.
Hypopnea
is partial airway obstruction lasting longer than 10 seconds with a
drop of oxygenation by 4%. There is usally at least a 30% decrease
in measured excursion of the chest when the airway is obstructed.

C. Health outcomes of OSA

Airway obstruction (complete or partial) causes a decrease in
oxygenation and can lead to serious consequences including daytime
drowsiness,
serious cardiovascular effects
including hypertension, irregular heartbeats, heart attacks, heart
failure, and stroke. Depression is not uncommon and being
chronically sleep deprived will certainly change your mood. Car
accidents are often associated with OSA.

D. Anatomy of an obstructed airway

With a patient sleeping on their back, especially during dream
sleep, the tongue and soft palate can fall on the back of their
throat obstructing the oral airway. Note the difference in a normal
patient and one with OSA in the images below. If the nasal airway is
stuffy or obstructed, it adds to the obstruction, but nasal airways
opened or closed cannot prevent obstruction of the airway. The
images clearly demonstrate this obstruction.

E. The cycle of obstruction is important to understand

Please follow this cycle of an obstructive event. This is what
happens when a person stops breathing every time, which commonly
occurs 30 or more times a hour.

With OSA, there is compromise somewhere in the upper airway usually
from a
large tongue, large tonsils, large neck circumference, elongated
soft palate, a short lower jaw, or a high arched palate.
Oral and pharyngeal obstruction can be aggravated by
nasal obstruction
(deviated nasal septum, allergic swelling, etc.) creating mouth
breathing, snoring, and ultimately worsening of apneic episodes.

OSA can cause
bruxism
(grinding the teeth) resulting in dental fractures, and failures of
dental implants.

The
drawing below
illustrates the various degrees of oral impairment in patients.
Note the relationship of the volume of the tongue to the capacity
of the oral cavity.

Snoring
really indicates partial upper airway obstruction and should be a
signal that there is some type of interference in the smooth flow of
air through the nose and mouth into the lungs. In contrast, if there
is lower airway obstruction (in the chest), there is noisy breathing
including stridor or wheezing, and struggling that is not relieved
with waking up.

F. Observation by family—high risk signs and symptoms

The
index of suspicion for OSA
needs to be high in anyone that snores, has daytime drowsiness,
diabetes, hypertension, heart disease, sleep disorders, daytime
drowsiness, and is overweight. Other signs might include waking up
tired, mood swings, noticing excessive daytime fatigue, morning
headaches, cognitive difficulties, or sexual dysfunction from sleep
deprivation (Viagra has been reported to aggravate OSA).

Women are twice as likely to not report snoring or apnea out of
embarrassment.

G. Testing for OSA—Home testing vs sleep lab

1. At-home sleep testing

There are at-home sleep apnea testers
(above photos) that are far from the quality of a certified
laboratory that evaluates patients for sleep apnea. It would serve
as a screening test only, but if a patient refuses an all-night
study in a certified sleep lab, or has no insurance, this might be
an alternative.

2. Sleep Laboratory Testing—Certified Sleep Disorders Centers

Neurologists, Pulmonary specialists,
and Ear, Nose, and Throat Surgeons play a key role in the evaluation
and treatment of these patients. They consult with certified sleep
centers to maintain the highest quality of study.

The sleep study must be read by a certified sleep specialist to
determine the presence, extent, and nature of the OSA. A complete
study is usually performed over 2 nights. The first night tests for
the extent and severity of OSA, and the second night to calibrate a
CPAP apparatus to find the pressure necessary to relieve the
obstruction.

A sleep study includes an
EEG
(brain wave test),
EKG
to pick up cardiac abnormalities, an
electro-oculogram
(determines REM-rapid eye movement-dream stage to correlate usually
with the worst time of the night for OSA), a
monitor for oxygen levels
in the blood(below 90% is considered harmful),
blood pressure
monitoring,
electromyogram
(to detect restless leg syndrome),
snoring sensors,
airflow monitoring
during respiration (sensor around chest wall), and a technician who
observes the patient while
monitoring all the electronic studies.
It is very important to validate all the physiological events
altered by apnea.

Discovering cardiac
arrhythmias(irregular heartbeat) or cardiac ischemia(impending
potential heart attack), how low the oxygen levels drop during an
episode, seizure activity and interference with sleep stages, number
of and length(#of seconds) of apneic episodes, blood pressure
elevation during an episode, and other events are necessary to
assess the full impact of apnea.

The death rate from this disease is difficult to calculate since
people that die in their sleep carry the answers to the grave. My
grandfather died of a stroke in his sleep but was very obese and had
severe snoring and apnea back before the syndrome was even really
known. How many night time heart attacks occur during an apneic
episode?

H. Treatment options for relief of OSA

Since I last reported on this subject, there are more appliances
and devices on the market. No question, CPAP (continuous positive
airway pressure) is the gold standard for treating OSA, but there
are many improvements you should know about. For those disappointed
their results with CPAP, please carefully read this report. If you
know someone who has OSA or is suspected of it, this information
could save their life(and get couples back in the same bed).

1. Medical management

Weight loss
is very effective in relieving some patient’s OSA. Do not forget
this. It will help lower the pressure necessary for CPAP to work
effectively. A very high pressure is difficult to tolerate.
Management of all medical conditions is a must including maintenance
of diabetes, cardiovascular disease, etc. The patient must not drink
alcohol or take sedating medication in the evening, as this will
aggravate OSA. This might include some antihistamines,
tranquilizers, and other medications that have sedation as a side
effect. Alcohol is one of the worst not to mention opiates, which
diminish respirations and lead to accidental death.

Researching these options is recommended. Many try to find an
alternative to CPAP without giving it a real chance. Clearly, it is
the best way to relieve airway obstruction especially those with a
thick short neck, a large tongue, and elongated palate/large
tonsils.

2. Oral appliances

If a person has dental/facial abnormalities (i.e. short lower or
upper jaw, high arched palate), a dental appliance to bring the
lower jaw forward a few millimeters, may be very effective with
snoring but rarely is adequate to relieve OSA. Going to a dental
specialist that custom makes these is critical.

Here are two options (above) of dental prostheses that pull the
lower jaw forward which assists in pulling the base of the tongue
off the back of the throat. These prostheses cost $300-2500. Some of
these are adjustable over time and may be a better option as a
person gets used to the appliance. Some could be incorporated into
the use of a CPAP machine, and may be necessary for CPAP to really
be effective.

There are TV ads trying to sell “one size fits all” dental
prostheses to treat snoring, but helping snoring is serious business
and needs customized care, and it still may not help apnea. A sleep
study needs to differentiate between snoring and apnea.

Oral appliances may help mild to moderate OSA in selected cases,
but is no substitute for CPAP. Any oral appliance must be studied in
a sleep lab to prove it is effective. About 50% are helped.

Many patients have failed to tolerate CPAP and given up. Perhaps
the addition of an oral appliance might be considered with
modifications for using both.

3. CPAP machines (Continuous positive airway pressure)

Below is a typical full face CPAP mask with the bedside monitor
power box. It is critical to try different masks to see which are
the most beneficial and yet tolerable.

Some of the newer models are much more quiet. Humidifiers attached
to the CPAP machines are strongly encouraged to keep the airway
moist.

Also, most of the newer machines have a monitoring device that
will sound off if the mask is removed. This is

important to notify the patient they have inadvertently removed
their mask.

The usual pressure necessary to relieve apnea episodes is 5-20 cm of
water pressure. Tolerance correlates with the amount of pressure. It
is imperative to raise the blood oxygen levels above 90% to be
considered successful.

There are now other options that use continuous flow of pressure. It
is called
BiPAP,
which provides 2 pressures, one for inspiration, and one for
expiration. This tends to be more tolerable.

Another option is
Auto-PAP,
which adjust the pressure while asleep using the least necessary
pressure.

Proof of use for companies and for continuing insurance coverage of
CPAP

Most insurance requires that the apparatus have a memory card for
the number of days and amount of hours per night, it is being used.
Many industries (like the truck industries) require a report be
submitted to the company for safety reasons to retain a driver’s
license. OSA and truck accidents (and car) are a big problem with
drivers falling asleep.

The
no-mask apparatus
has nasal cannulas that force air into the nostrils to relieve mild
obstruction or snoring, but would be a poor option with most with
moderate or severe apnea.

Regardless of choice, the benefit must be verified in a sleep lab to
prove its value in relieving deoxygenation and apnea. If it only
helps partially, the physiologic risks continue.

Adherence
using CPAP is critical.
Suggestions to increase usage are:

1) Attend group classes at a sleep center to find out ways to
improve tolerance. 2) Reinforcement and understanding by the family
(and doctors) to encourage compliance by the patient and emphasize
how critical it is to relieve OSA 3) Staying in touch with the
respiratory center where the CPAP was purchased to have questions
and concerns answered 4) Use alternative masks if not satisfied 5)
Use a cool mist humidifier attached to the CPAP machine to relieve
dryness in the airway 6) Prompt attention to nasal congestion, sinus
issues, etc. 7) Losing weight is critical, so a weight management
plan must be started 8)Monitors for use and memory cards in the
machine 9)Don’t give up.

Medicaid and Medicare will pay for 12 weeks of CPAP initially, and
if there is improvement determined by the lab, further coverage will
occur with periodic reports of use from the memory cards now
installed in the machines must be submitted for certification of
proper use.

3
options for masks shown below:

The larger mask will be necessary for those with a higher CPAP
pressure necessary to relieve the obstruction of the airway. The
mask must fit snuggly to prevent air escape.

There is a new cleaning apparatus for CPAP masks that could be
valuable.
TrySoClean.com
is the website.

4. Surgery for OSA

Having had great success with surgical management of OSA while in
practice, I encourage a consultation with an experienced surgeon
just to get information. I always encouraged patients to try CPAP
and/or an oral appliance before considering surgery(and lose
weight). Careful selection is critical to expect good results.

Having had great success with surgical management of OSA while in
practice, I encourage a consultation with an experienced surgeon
just to get information. I always encouraged patients to try CPAP
and/or an oral appliance before considering surgery(and lose
weight). Careful selection is critical to expect good results.

a)UVPP--The
gold standard of surgery involves removing selected portions of the
soft palate, removing the tonsils, and removing redundant portions
of the lining of the each sides of the throat if they excessive.
UVPP means
uvulo-pharyngo-palatoplasty.

b)
Removal of the tonsils and adenoids
will relieve snoring and OSA in many children (having cured many
kids with airway obstruction over 30 years). In my personal
experience, it frequently relieved a child’s hyperactivity. Although
not proven there must be an association with OSA and airway
obstruction.

c)If facial and jaw abnormalities are present,
orthognathic surgery
(surgical
movement of the jaws forward or backward) may be required. Below are
examples of moving the lower jaw forward (left image) and both upper
and lower jaws (right image).

d)
Snoring procedures--There
are snoring procedures that tighten the soft palate with a
radiofrequency wave ablation apparatus. Just removing the uvula will
also relieve snoring in many. I performed that procedure with a YAG
laser in the office very successfully. Also plastic implants can be
inserted into the soft palate and may help snoring to make the soft
palate more rigid, but may alter the tone of the voice as can any
surgical procedure.

Palatal implants Septal nasal surgery

e)
Nasal surgery
is often a necessary adjunctive surgical procedure(s). Mouth
breathing is a clue to an issue in the nose. Frequently, allergies
must be managed as well. The surgical procedure involves improving
the nasal airway by straightening the nasal septum and reducing the
size of the turbinates (see above drawing). I discussed this
previously including sinus surgery.

f)
Genioglossus Advancement
involves removing a small portion of the lower jaw where the tongue
is attached to the inside of the lower jaw, and advancing the tongue
forward through an opening created in the lower jaw. This is
demonstrated in the drawings below. The goal of this surgery is to
move the tongue away from the back of the throat, which obstructs
the airway causing OSA.

g)
Palatal widening
procedures also allow the tongue to rest in the roof of the mouth,
which assists keeping the tongue from falling back into the throat
obstructing the airway during sleep. If a child is a mouth breather,
they will not position the tongue correctly in the mouth thus
allowing the palate to not widen correctly creating airway
obstruction and a long face syndrome.

In a child, before the hard palate has stopped growing, a palatal
widening apparatus can actually widen the palate as it grows to
relieve a high arched palate. Over time, the width can be increased
by the orthodontist by adjusting the hardware. In an adolescent or
adult, surgery can accomplish the widening.

h)
Tracheostomy
in morbidly obese patients may be the only option. A permanent
tracheostomy tube is placed in the neck. During the day, the stoma
can be plugged, but at night, the plug is removed to allow free
breathing by the patient.

i)
Weight loss (Bariatric) surgery
is also now an option for OSA, and a very successful method of
addressing obesity and can even reverse type 2 diabetes. For optimum
results of OSA treatment, weight loss must be addressed. For a full
discussion on obesity, go to reports 44-48, and bariatric surgery
click on:

OSA is also known to increase intra-ocular pressure. There are
multiple eye conditions that are associated with OSA including
floppy eyelid syndrome, keratitis, keratoconus, conjunctivitis,
papilledema, and optic neuropathy. It does not increase the risk of
glaucoma rather if you have it or are prone to it, OSA can make it
worse and more difficult to treat. If you have OSA, tell your
glaucoma doctor and your OSA doctor. They may not be aware of the
connection.

Recent studies have analyzed whether CPAP can reverse the
cardiovascular consequences of obstructive sleep apnea. It has been
reported to decrease blood pressure in more severe OSA patients, but
sadly, after following these patients for 3.7 years in a recent
study, using CPAP for an average of 3.3 hours per night,
the endpoint for heart attacks, strokes, heart failure, and angina
did not move.
However, it did improve daytime drowsiness and quality of life, less
snoring, and mood. If patients used CPAP the entire night, these
results might be different.

The problem with CPAP is keeping it in place all night. Many
patients remove it while asleep. Most studies report 2-4 hours of
continuous use is about the norm, and therefore, half or more of the
night, the patient is not protected. However, a recent study
reported 68% of patients were using their CPAP regularly after 5
years. OSA does not go away. This is a life-long commitment. Giving
up on treatment will only aggravate symptoms and continue to create
serious health problems. If that happens, consideration for
alternative methods including surgery is indicated.

The need for
management of existing medical issues including excessive weight
aggressively is critical to prevent a complication.

Surgical results depend on the technique used, experience of the
surgeon, additional weight loss, and supplemental CPAP. In my hands,
improvement with most of my patients reduced by at least half of
their apneic episodes. Oxygenation was brought back to safer levels,
and the patient always was relieved of daytime drowsiness, and
improved their quality of life. However, some still had to use CPAP,
but with lower pressure settings, which makes it more tolerable.
Also continued weight loss was emphasized.

K. New medical treatments for daytime drowsiness

Residual fatigue and daytime drowsiness may be treated with brain
stimulants-- either modafinil (Provigil) or armodafinil (Nuvigil).

Monitoring of the patient’s weight is very important, as weight
gain can affect how much pressure is necessary to relieve OSA with
CPAP.

L. THE BOTTOM LINE!

Unless, a person is cured of a significant number of apneic
episodes by losing excessive weight, relieving anatomical
abnormalities with surgery or dental prostheses, getting the blood
oxygen levels above 90%, and wear CPAP all night, the
reduction of cardiovascular disease may not occur.

This subject is on the minds of most Americans. It is such a complex
issue. We continually are caught between Big Pharma(PhRMA)— --
saying they need these prices high to cover their expenses for
research and development and Americans wanting reasonably priced
drugs. In fact, we are paying more
because our government allows it. We are also paying for all
their failures. Only 5 in 5000 drugs that enter preclinical testing
progress to human testing, and only 1 in 5 of those are actually FDA
approved.

Pharmaceutical companies are sending big checks to politicians.
The company, Mallinckrodt spent $44,000 in contributions in the
first quarter of 2017 to congressmen. They also spent $610,000 on
lobbying efforts for Congress (Democrats and Republicans). They are
responsible for making one of the most popular pain medications
(fueling the opioid crisis), and recently marketed their multiple
sclerosis drug for $34,000 (Acthar) a vial ($162,317 per year) in
2015 according to Kaiser Health News. It was Medicare’s most
expensive drug per patient in 2015, making up a third of the revenue
of the company. It cost $40 a vial in 2001. It’s legal home is
Ireland evading taxes in the U.S.

President Trump is asking for cooperation from Congress on this
terrible issue, but even the Republicans do not uniformly support
him. They are more interested in their own skin and their own
pocketbook. Drain the swamp!!

Sanofi and Pfizer pharmaceutical companies top the list of donors
to Congress according to The Financial Times. At the same time, this
company was even called out by the pharmaceutical industry for not
spending enough on research.

Mallinckrodt was fined by the Federal Trade Commission $100
million because of the drug Acthar having illegally quashed
competition for MS (multiple sclerosis) drugs.

When congressmen are seeking re-election, they get very aggressive
in soliciting money from any source.
Ask your congressman how much money he gets from Big Pharma!

Cost of prescription drugs

In 2015, CMS (Centers for Medicare and Medicaid Services) reported
that prescription costs account for 10% of the healthcare dollar
increasing 9% more to $324.6 billion.

The new extremely expensive cancer
drugs account for more than 50% of the cost of all drugs on the
market. These outrageously expensive drugs are going to
increase 20% per year for the next few years, according to the
cancer organization (ASCO—American Society of Clinical Oncology).
Compare the price of prescription
medications (9%) to the total of cost of Medicare (20%) and Medicaid
(17%) to the total healthcare dollar, while total healthcare
costs are currently 17.8% of GDP.

Overall cost of healthcare

The total cost for healthcare was $3.2 trillion in 2015 and is
expected to cost $3.35 trillion this year.
Slightly less than 10% of people in this country are uninsured. The
cost for healthcare coverage in 2015 was just under $10,000 per year
per person. If 2017 figures were available, it would be well over
the $10,000 figure. The costs are projected to rise 5.8% per year
from 2015-2025.

Big Pharma

Big Pharma-phRMA(Pharmaceutical Research and Manufacturers of
America) is the name commonly used to identify the pharmaceutical
industry. The 11 largest global drug companies made $711 billion
over 10 years ending in 2012 according to Healthcare for America
Now. Thanks to our government not negotiating Medicare prices, our
cost is about 40% higher than Canada and 75% greater than Japan. The
feds negotiate prices (about 20% discount) for Medicaid but not
Medicare. You can point your finger directly to the lobbyists and
congressmen who are getting contributions for their campaigns.
(Drain the Swamp).

Our doctors prescribe more than most country’s doctors, while
patients have learned over time to be extremely dependent on a pill
to cure everything. There is plenty of blame to go around.

New York State Legislature is working on a system to curb Medicare
prescription costs (we will see how successful they are).

In 2014, the total revenue for the
pharmaceutical industry exceeded $1 trillion dollars for the first
time. Pfizer is #1 and had a total revenue of $53 billion.
Pfizer makes Viagra, Viracept for HIV, Xalatan for glaucoma, Xanax
for anxiety, and Lyrica for pain, seizures, peripheral neuropathy,
restless legs, etc. to name a few of the big hitters.

Consumers have learned to request generic drugs, we are now facing
insurance companies that won’t pay for generics, rather they only
pay for the brand name drug which requires a much higher co-pay.
This does not make sense unless you realize that once again big
corporations are teaming up to keep the price of drugs high and
fatten their pockets. The pharmacy
distribution and benefit managers may be in the middle of
this as they control distribution of drugs to pharmacies. Insurance
companies are either getting paid under the table or there is some
multilayered cover up. This was front page news in the New York
Times on August 6, 2017.

Atorvastatin and Xetia are two examples of generics. These are off
patent and should be costing much less, yet my copay was $300 for 90
days for these drugs. Some insurance companies will pay for the
brand names instead of the generic alternative. What for?? $$$$$$

Be sure your doctor is prescribing
generics. CVS Caremark (CVS Silver Script is one of CVS’
insurance companies), one of the largest benefit managers sent a
memo to pharmacies informing them that some of the Medicare
prescription drug plans would cover only brand name drugs. I have no
answer. There is such aneed to reform healthcare (even Medicare).

President Trump supports healthcare reform but nothing has
happened, thanks to disarray in the Republican Party. There are
those that want everything to go their wy or they will not vote for
reform. Without fixing our problems, the costs will continue to
escalate, and we will eventually be forced into single payer
healthcare. Can our economy withstand single payer?

By the way, now that most doctors are employees, many are ok with
single payer (including academic centers and organized medicine).
They are on salary so any plan that pays for every bill, why would
they not be ok worth it? Call your Congressman about negotiating
Medicare prescription prices with Big Pharma. There is nothing we
can do about doctors being run out of private practice (because of
regulations and enormous administrative costs). Mergers of practices
are happening everyday. Centers like NorthEast Georgia Center in
Gainesville, Georgia controls the northeast part of the state now,
and Angel Hospitals form Asheville control Western North Carolina.
There is no competition. You know what that means. These centers can
charge what they want for medications.

Brand vs generic drugs

After a patent is lost for exclusive distribution of a drug, a
brand drug can be produced and distributed as a generic duplicate.
It is no longer being produced by the brand name company. There are
pharmaceutical companies that do that.

Why then are there continued high costs for these off-patent drugs
up to a year after the drug can be produced as a generic? The
answer---there is a delay in getting those generics?
The brand name companies pay the
generic companies to delay production of a generic or the generic
companies are paid to produce lower numbers of these drugs for a
year and longer!! A significant number of these generic
companies are not based in the U.S. and out of the direct
jurisdiction by the FDA.

90% of drugs prescribed are generic. However, if only 1 company
is making a generic equivalent, they can corner the market and
charge higher prices. Some of these generics have risen as much as
1000% over 6 years. And our government is letting them get away with
it. NEJM Journal Watch, July, 2017

My wife takes a weekly shot for a disease and that drug (Avonex)
that has been around for 20 years is still costing us $1000 a month
(insurance pays $4000). There is no generic equivalent.

Our government paid $173 million a French company (Sanofi) to
develop the vaccine for Zika virus development and production was
funded by the U.S. Government, and gave them exclusive rights to
distribute it. Our government gave them the right to charge whatever
they choose and we paid for it. Does that make sense? And some
people want more government control and even have governmental
control all of healthcare.

President Trump has got to ban lobbyists lining the pockets of our
congressmen, but how do we get the US Congress to do this when their
pockets are being lined by Big Pharma? Congress also must vote to
negotiate prices for Medicare like they do Medicaid. The whole
system must be reformed including the FDA. We the people must
insist!!

Specialty Drugs are where the big bucks are today

Actually the big money for Big Pharma today is switching from
brand name drugs to a class of drugs called specialty drugs (IV
cancer drugs-immunotherapy-Opdivo, Yervoy, etc., arthritic drugs (Remicade,
Humira, etc). The cost rises as most physicians are now employed so
hospitals and clinics will be buying these specialty drugs directly
and billing insurance higher prices (estimated to be 20% higher than
when physicians bought these drugs).

Example of Brand drugs that are ridiculously expensive

The medication to treat hepatitis C (Sovaldi) is $1000 a pill
(regimen is a pill a day for 12-24 weeks=$168,000 for the potential
cure (96% cure rate) and 2.7 million Americans have been diagnosed
with Hep C.

Generic Group sues the state of Maryland for keeping generic drug
prices low

The main U.S. trade group for generic pharmaceutical companies
filed a lawsuit recently against the State of Maryland blocking the
state attorney from keeping generic drug prices low on Medicaid
patients that included a $10,000 fine for price gouging. This is
what we are up against. Even the generic companies are using our
constitution to prevent the American people from getting reasonably
priced medications. The courts will rule this month.

A recent article from the NEJM (July, 2017) stated that over 50 of
the most popular older generic drugs have increased in price by 400%
between 2012-2015.

Drug Shortages (real or not?)

Antibiotics are some of the most common drugs in short supply.
Epinephrine, atropine, cortisone, albuterol inhalers, lidocaine,
nitrous oxide, and many other injectable medications primarily used
in the hospital are often backordered due to shortages. The FDA is
working to resolve these shortages and are having some success. If
these smaller companies are being paid big bucks to delay
distribution, that must be stopped. Fines have been levied against
some companies.

Pharmaceutical Distribution Management—another cost in the price of
a drug

There is always a middle man in business. The pharmaceutical
companies must store and distribute these medications to over
200,000 U.S. pharmacies. However, they do not do this….there are
distribution centers to facilitate this. It also must supply
hospitals, clinics, and long term care facilities in the U.S. There
are major distribution centers around the country that perform this
massive task and it is big business.

There are three major companies
that monopolize this industry—AmerisourceBergen, Cardinal
Health, and McKesson Corp. The combined
2016 revenue for these three companies was $378.4 billion and
this year is expected to surpass $400 billion.

The consolidation of major national companies with mergers is
pressuring wholesale prices to rise. Some of the major players are
CVS, Walgreen’s, Walmart, Rite-Aid, and United Health Group.
Walgreen’s actually owns ¼ of the number one distribution center
(AmerisourceBergen). Mergers usually mean higher prices.

Healthcare could be less expensive, but as long as our government
is in bed with Big Pharma, we are up a creek. And who is regulating
these distribution centers, and think what will happen if the
government runs all of our healthcare with all the outside
influences buying the loyalties of our Congress.

The New York Times, July, 2017

NEJM—various articles

Drugs from Canada

A recent poll stated that 8% of Americans are getting their
prescriptions from Canada or other countries. Although illegal, our
government (FDA) has not enforced the law. There has been
legislation to authorize broader importation from Canada, but has
never gained traction at the federal or state level (can you say
lobbyists?). In fact, the 2003 Medicare Modernization Act enacted
Part D, and included a provision to allow importation of drugs from
Canada if they are safe and could save money. Senator Bernie Sanders
proposed legislation for implementing this provision but was voted
down by other U.S. Senators, because of concern about safety from
the FDA (by law they must be equivalent. Tell me Big Pharma is not
behind keeping Canadian drugs out of our country!

The Canadian government has even offered to pay a user fee to
provide extra safety measures for drugs coming to the U.S. and yet
they are not officially legal to be sold here. Drain the Swamp!!

In the two previous reports, I have discussed the blood system and
diseases of the red blood cells. This report will discuss white
blood cells and platelets, the other components of the solid portion
of blood. The other component of blood is the liquid portion,
plasma, and to complete the series, blood transfusions (red cell and
plasma) will be discussed in January after leukemia and lymphoma is
discussed.

Most people make 1 billion white blood cells daily. The white blood
count is an indication of how well the body responds to infections.
With any acute infection, the white blood cells elevate to respond.
The type of white cell elevation may hint at the cause of the
infection (bacterial, viral, fungal, parasitic, etc.) The white
cells travel to any infection site to fight the infection and try to
keep it from spreading.

A. Leukocytosis--elevation
of the white cells--causes

a) Infection--A
count higher than 11,000 is considered high. If a patient has an
infection (especially bacterial), it is expected that the body
increases the white cell count. If it does not, this may indicate
more serious underlying diseases and a poor response to an
infection.

b) Drug and acute allergic reaction—medications
may increase the white count in response to the challenge of an
allergic reaction, especially if it is a sudden reaction, such as a
penicillin reaction. Also acute allergic reactions from food,
pollens, mold, etc. may create an elevated white count with specific
types of white cells.

c) Diseases of the bone marrow—diseases
of the marrow may be the cause for a elevated white count. When this
occurs, there is a concern for leukemia.

d) Immune system disorder—an
elevated white count may occur with an underlying immune disorder.
Rheumatoid arthritis may elevate the white count with an increase in
lymphocytes.

Lymphocytes
elevate to increase an immune response with antibodies to fight
infections and immune diseases.

Basophils
secrete certain chemical that alert the body to the presence of an
infection and elevate in allergic reactions.

Eosinophils
elevate in a reaction from parasitic infections, cancer, and
allergic reactions.

Monocytes
breakdown the walls of bacteria in fighting the infection.

C. Leukopenia (neutropenia)--Reduced
white cell count

a) Definition

When the white cell count drops below
4,000, this may be a cause for concern, as it may indicate a
poor immune response to an infection or reaction. Certain diseases
should be ruled out such as HIV-AIDS, certain viral infections, and
an underlying illness such as lupus, Sjogren’s disease, Lyme
disease, etc.

The most common white cell to be decreased is the
neutrophil, hence the word
neutropenia (penia means less).
However, any type of white cell may be decreased due to certain
circumstances. For instance, if there are decreased lymphocytes (lymphopenia),
viral infections and immunosuppressed patients may be the cause.
Just as in red cell diseases, leukopenia can be caused by a drop in
production of white cells by the bone marrow or actual destruction
of the white cells. There are multiple causes.

b) Causes of leukopenia

Chemotherapy, immune medications for diseases such as multiple
sclerosis, radiation, myelofibrosis, aplastic anemia, leukemia, and
viral infections all can cause a low white count. Cancer treatments
that cause leukopenia may require a drug to stimulate the white cell
or the red cell production. If the white count remains low, the
patients are at serious risk for an overwhelming infection which can
be lethal. Chemotherapy, for instance, may have to be stopped
temporarily because of it.

There are medications that can stimulate bone marrow production of
white cells (granulocyte colony
stimulating factor), and chemotherapy in particular can
interfere with this protein. Neupogen,
Neulasta, Leukine, and Prokine are medications to act like
(called agonists) the granulocyte colony stimulating factor to
stimulate the bone marrow to accelerate the production of white
cells. These medications may be given 24 hours before chemotherapy
to help prevent the side effect of leukopenia.

These medications are extremely expensive and do have some
significant side effects including spleen rupture (from stimulating
the spleen to make white cells), serious lung disorder (ARDS), and
allergic reaction.

II. Platelet Disorders

Platelets are not actually complete cells. They are cell fragments
primarily composed of proteins. Like other blood components, their
numbers are controlled by a protein manufactured by the liver called
thrombopoietin, which stimulates
a bone marrow cell called megakerocytes.
This cell extrudes platelets from the cytoplasm, which circulate in
the system to be called up by the body to assist in clotting when
bleeding occurs. There is a protein in the platelets that attracts
other platelets to form aggregates for participating in the
formation of a clot. In the left slide below, one can see platelets
(little dots) inside the megakerocyte, which are expelled out of
that cell. On the right is an abnormal megakerocyte(leukemia). Both
slides are from a bone marrow biopsy.

For a demonstration video on how platelets assist in plugging a cut
or tear in a blood vessel, click on:

As many as a third of the blood’s platelets reside in the spleen
ready to mobilize when called. Platelets have a life span of 7-10
days.

The normal platelet count is 140,000-400,000. Too few or too many
create trouble.

Platelet disorders create problems with hemostasis. This term is
the body’s mechanism of keeping a balance between clotting and
bleeding.

There are 4 basics issues to discuss regarding platelets

1. Abnormal increases in platelets (thrombocytosis/thrombocythemia)

2. Decrease in platelets (thrombocytopenia)

3. Platelet dysfunction

4. Medications that affect the platelet on purpose

1. Abnormal increases

Previously, I described a term called
myeloproliferative neoplasms. These are malignant causes of
increases in blood cells (polycythemia
vera, myelodysplasia, and thrombocythemia). When these cells
are produced abnormally by the bone marrow, these diseases occur.

Thrombocythemia is rare and causes problems with abnormal clotting
and strokes. These patients can progress to polycythemia vera,
myelofibrosis (scarring of the bone marrow), or leukemia.

Medications to decrease thrombocythemia

Interferon, Anagrelide, or hydroxyurea
are used depending on the patient.
Aspirin is also used to prevent
clots. Keep in mind anticoagulants do not affect platelets (they
interfere with clotting factors).

2. Decrease in platelets (thrombocytopenia)--Causes

a) Idiopathic thrombocytopenic purpura (ITP)

This disease is an autoimmune disorder caused by antibodies
against their own platelets. The cause is unknown (hence the word
idiopathic), although occasionally occurs in patients with lupus and
HIV. It is also a complication of hepatitis C.

b) Acute ITP, an autoimmune disease,
occurs in children, while the chronic form occurs mainly in adults.
The acute form usually occurs after a viral infection (even
infectious mononucleosis) and is self-limited, and it presents with
bleeding in the skin, mouth, and retinal (eyes) hemorrhages. The
lymph nodes and spleen enlarge.

The chronic form usually occurs in 20-40 year olds. It occurs more
frequently in females, can occur during pregnancy, and after a
transfusion.

The above photo is a classic appearance of a patient who bleeds into
the skin from low platelets (called purpura).

Heparin-induced thrombocytopenia (the most common drug that can
induce thrombocytopenia)—it can occur in 5-8% of cases of those who
are given heparin.

Heparin is a commonly administered anticoagulant after major
surgery especially cardiovascular and orthopedic surgery. There are
two types of reaction--immune mediated and non-immune. The immune
mediated type causes a drop in platelets with potential for bleeding
and the other non-immune type causes a direct reaction between
platelets and heparin causing clumping of platelets and thrombosis (clotting).One
of my former neurosurgery partners (in my multispecialty group)
developed this after being given heparin after heart surgery, which
suddenly created a clot in his lower leg and resulted in him losing
his lower leg.

Today, this crisis is treated with oral anticoagulants to prevent
clots in the non-immune type without causing excessive bleeding.
Drugs such as Xarelto do not react with the platelets in the way
heparin does.

d) Thrombotic thrombocytopenic purpura (TTP)

This rare disease is a very serious disorder characterized by fever,
neurologic symptoms, kidney failure, and bleeding. This disease can
also occur in autoimmune disorders, pregnancy, HIV, and caused by
medications. Again, patients frequently report a flu-like syndrome
2-3 weeks prior to the onset of TTP. (There is a hemolytic uremic
syndrome that mimics TTP).

Treatment of low platelets disorders

There are medications that can stimulate the bone marrow to
produce more platelets.

Options depend on the disease and circumstance:

a)Treat the underlying disease and or stop a suspected
medication

b)Blood or platelet transfusions

c)Medications-corticosteroids
will boost the platelet count, and if that is not successful, there
are medications to suppress the immune system, such as lithium
carbonate or folate may recommended. Eltrombopag (Promacta)
is used for autioimmune and hepatitis C cases. This drug mimics the
effect of the protein substance that normally stimulates the bone
marrow platelets (thrombopoeitin).
Others include Nplate and
Neumega. These drugs are also
used in aplastic anemia, since this disease has low red and white
cells, and platelets. There should be a response(rising platelet
count) in 1-2 weeks.

d)Surgery- splenectomy--removing
the spleen may be successful since as much as one third of the
platelets are present in the spleen. If the spleen is enlarged, this
may need to be performed, and it is possible the spleen may be
chewing up the platelets as part of the pathology of the disease,
rapidly making more creating an enlarged spleen. I have not
discussed the spleen but will do so when talking about leukemia.

e)Plasma exchange—plasmapheresis
is used to remove the plasma part of blood out and replace it with a
substitute plasma richer in platelets.

3. Functional disorders of the platelets-platelet dysfunction

There are relatively rare disorders of the platelets which can be
hard to diagnose until a person has surgery and the clotting
mechanism is called to do its job and doesn’t. That is why clotting
studies and a platelet count are performed prior to certain
surgeries (in ENT and other procedures, it is commonplace).

Von Willebrand’s disease is a
common inherited bleeding disorder found in 1 out of a 1000 people.
These patients usually have not had bleeding and bruising issues
like in hemophilia. I have diagnosed this in a couple of patients
with nosebleeds. The platelets have an abnormal protein that does
not allow normal stickiness of platelets and therefore aren’t as
efficient in forming clots. This disorder is similar to hemophilia
and actually makes factor VIII (the clotting defect in hemophilia)
less effective in the clotting mechanism. This is an important minor
bleeding disorder but becomes an issue with patients who have
surgery, and can cause excessive menstrual periods.

There are many other rare bleeding disorders but not of enough
importance to enumerate.

4.
Medications to prevent clotting by affecting platelets

Aspirin and NSAIDs cause platelets to lose their stickiness by
affecting the protein (thromboxane) responsible for platelets
sticking to each other. This is one of the methods used to “thin”
the blood and prevent clotting of stents, heart valves, etc. Long
term use of these over the counter meds can often be used instead of
oral anticoagulants. I take 325mg of aspirin a day for life to
prevent clotting of a carotid artery stent placed for radiation
induced stenosis.

Peripheral arterial disease (PAD) of the extremities affects 8
million Americans over the age of 40.

Risk factors for PAD are
essentially the same as for any cardiovascular disease to include
smoking, diabetes, lipid elevation, hypertension, family history,
male, black, over weight, and aging. Smoking and diabetes provide a
3-4 fold increased risk.

Symptoms include claudication
(pain in the calf on exertion(see below), being relieved by rest
similar to angina of the heart. Hair loss below the knee is common,
and with more advanced disease delayed healing below the knee. In
diabetics, foot ulcers can occur.

Diagnosis

Physical exam—If
there is good blood flow into the foot a small artery (dorsalis
pedis) can be felt beating on front of the foot and behind the inner
ankle bone (posterior tibial artery). The drawing shows the dorsalis
pedis artery (arrow).

Posterior tibial artety

Also, there is an artery just behind the medial malleolus (inside
ankle bone) called the posterior tibial
artery. If those pulses are poor or absent, there are more
tests that can define PAD.

Ankle-brachial index test(above
left)—a blood pressure cuff is attached at the calf and arm
(brachial artery) and with the aid of an ultrasound machine, the
cuff pressure is raised on both. The pressure necessary to occlude
the blood flow in the thigh and calf is measured and should be about
the same as the arm. If the calf vessel occludes sooner by greater
than 15%, there is PAD present.

Pulse volume recordings
(above right) (PVR)

This test is a simple screening test, measuring the changes in
blood volume at various locations along the leg with the cuff pumped
up to 40-60 mm Hgb.

Arteriography
will delineate the actual location of partial or complete occlusion.
The arteries come off the aorta to the femoral arteries in the thigh
and then to the popliteal and anterior tibial arteries splitting
further as shown.

Without blood supply to the lower legs, gangrene can from death of
tissue causing serious sickness. This is an example above, and is a
significant risk for diabetics and smokers with vascular disease.

Treatment

Often a diagnostic procedure (arteriography) can be combined with
an angioplasty. A balloon is
inserted into the leg artery (femoral artery in the groin, and can
dilate the constricted area and/or placement of a stent can be
placed).

Arteriography with Angioplasty

On the next page, the first image demonstrates the technique of
insertion of the vascular catheter, dilation with the balloon and
insertion of a stent.

Stent placement drawing below

The arteriogram on the next page demonstrates blockage on the left
photo. The middle photo shows the balloon in place dilating the
vessel. The panel on the right shows good blood flow through the
femoral artery.